EBV has been detected in epithelial cells in a new type of oral leukoplakia known as "hairy" leukoplakia (HLP). HLP is a harbinger for the development of acquired immunodeficiency syndrome (AIDS). In contrast to the lymphoproliferative syndrome (AIDS). In contrast to the lymphoproliferative syndromes which develop in the immunosuppressed in which the EBV infection induces cell growth and is predominantly non permissive for viral replication, in HLP the infection is permissive of EBV replication. The preliminary data obtained in this laboratory suggest that multiple strains of EBV of both the A and B subtypes are replicating in HLP tissue. Superinfection may contribute to the acute, lytic nature of the infection. The proposed studies will identify and characterize the strains of EBV which are replicating on the tongue in HLP, determine if an endogenous strain can be detected in episomal DNA from HLP tissue, and identify the strains which are present in the peripheral blood. The strains present in the infected tissue will be captured in lymphoid cell lines. These data will determine if HLP results from reactivated latent infection or represents an acute lytic process which is induced by superinfection with exogenous strains. The data will also increase our understanding of the process of reactivation of latent EBV infection and patterns of viral spread. In addition, potentially lytic or epithelial- trophic isolates of EBV may be captured for biologic and biochemical characterization. HLP provides a unique opportunity to further characterize EBV-epithelial cell infections at the molecular level. This knowledge, in conjunction with the clinical studies, will illuminate the complex interaction of EBV with the immune system.